The overall goal of Project 0005 (Human Studies) is to design, implement, and carry out Phase I and II clinical radioimmunotherapy trials using chimeric radiolabeled anti-CEA antibodies developed at the City of Hope. All potential agents will undergo screening through a radioimmunoimaging trial to examine for each agent: 1) its tumor targeting potential, 2) its clearance rates from normal tissue and anticipated toxicity, and 3) the incidence and duration of anti-antibody response, if any. Agents that will be serially tested include, chimeric T84.66 (high-affinity) anti-CEA monoclonal antibody (MAB), chimeric T84.66 fragments, chimeric T84.12 (low-affinity) anti-CEA MAB, and chimeric antibodies with novel chelates (macrocyclics and carboborane derivatives) containing other radionuclides (e.g. Cu-67). Each agent will be serially tested through imaging trials and move on to therapy trials in patients with metastatic CEA-producing malignancies. Initial imaging trails will utilize Indium- 111 radiolabeled antibodies, while initial therapy trials will utilize Yttrium-90 radiolabeled anti-CEA antibodies. Chimeric T84.66 will be the first antibody used. Therapy trials will acquire and analyze data on toxicity, tumor response, biodistribution, pharmacokinetics, dosimetry, and anti-antibody response. We anticipate completion of three to four therapy trials over the four year proposal period.